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The temporal program of DNA replication: new insights into old questions

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Abstract

During the last decades it has been shown that the replication timing program in metazoans is related to chromosome structure, the nuclear positioning and AT/GC content of chromosomal loci, their patterns of histone modifications, and their transcriptional regulation. Here, the current state of knowledge concerning these relationships is reviewed. An integrated view on structure–function relationships in the nucleus is provided and the determination and functional role of the replication timing program is discussed in this context. A corresponding comprehensive model is developed and a key aspect of this model is the suggestion that mammalian chromosomes are organized into stable units equivalent to replicon clusters. It is proposed that the nuclear positions of these units would depend on their histone modifications and determine the replication timing of the whole unit. It is furthermore predicted that replication timing is only indirectly linked to transcriptional regulation and contributes to the maintenance of gene expression patterns. These clear predictions, and the fact that the tools are at hand now to further test them, open an avenue towards solving the long standing problem on how replication timing is determined in metazoan cells.

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References

  • Alexandrova O, Solovei I, Cremer T, David CN (2003) Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra. Chromosoma 112:190–200

    Article  PubMed  CAS  Google Scholar 

  • Azuara V, Brown KE, Williams RRE, Webb N, Dillon N, Festenstein R, Buckle V, Merkenschlager M, Fisher AG (2003) Heritable gene silencing in lymphocytes delays chromatid resolution without affecting the timing of DNA replication. Nat Cell Biol 5:668–674

    Article  PubMed  CAS  Google Scholar 

  • Berezney R, Mortillaro MJ, Ma H, Wei X, Samarabandu J, (1995) The nuclear matrix: a structural milieu for genomic function. Int Rev Cytol 162A:1–65

    Article  PubMed  CAS  Google Scholar 

  • Berezney R, Dubey DD, Huberman JA (2000) Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci. Chromosoma 108:471–484

    Article  PubMed  CAS  Google Scholar 

  • Branco MR, Pombo A (2006) Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol (in press)

  • Brown KE, Amoils S, Horn JM, Buckle V, Higgs DR, Merkenschlager M, Fisher AG (2001) Expression of α- and β-globin genes occurs within different nuclear domains in haemopoietic cells. Nat Cell Biol 3:602–606

    Article  PubMed  CAS  Google Scholar 

  • Camargo M, Cervenka J (1982) Patterns of DNA replication of human chromosomes: II. Replication map and replication model. Am J Hum Genet 34:757–780

    PubMed  CAS  Google Scholar 

  • Caron H, van Schaik B, van der Mee M, Baas F, Riggins G, van Sluis P, Hermus MC, van Asperen R, Boon K, Voute PA, Heisterkamp S, van Kampen A, Versteeg R (2001) The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291:1289–1292

    Article  PubMed  CAS  Google Scholar 

  • Chambeyron S, Bickmore WA (2004) Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev 18:1119–1130

    Article  PubMed  CAS  Google Scholar 

  • Chambeyron S, Da Silva NR, Lawson KA, Bickmore WA (2005) Nuclear re-organisation of the Hoxb complex during mouse embryonic development. Development 132:2215–2223

    Article  PubMed  CAS  Google Scholar 

  • Chaumeil J, Okamoto I, Guggiari M, Heard E (2002) Integrated kinetics of X chromosome inactivation in differentiating embryonic stem cells. Cytogenet Genome Res 99:75–84

    Article  PubMed  CAS  Google Scholar 

  • Christen R, Braconnot J-C (1998) The biology of pelagic tunicates. Oxford University Press, New York

    Google Scholar 

  • Chubb JR, Boyle S, Perry P, Bickmore WA (2002) Chromatin motion is constrained by association with nuclear compartments in human cells. J Cell Biol 12:439–445

    CAS  Google Scholar 

  • Cimbora DM, Groudine M (2001) The control of mammalian DNA replication: a brief history of space and timing. Cell 104:643–646

    PubMed  CAS  Google Scholar 

  • Cimbora DM, Schubeler D, Reik A, Hamilton J, Francastel C, Epner EM, Groudine M (2000) Long-distance control of origin choice and replication timing in the human beta-globin locus are independent of the locus control region. Mol Cell Biol 20:5581–5591

    Article  PubMed  CAS  Google Scholar 

  • Craig JM, Bickmore WA (1993) Chromosome bands—flavours to savour. BioEssays 15:349–354

    Article  PubMed  CAS  Google Scholar 

  • Craig JM, Bickmore WA (1994) The distribution of CpG islands in mammalian chromosomes. Nat Genet 7:376–382

    Article  PubMed  CAS  Google Scholar 

  • Dimitrova D, Berezney R (2002) The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells. J Cell Sci 115:4037–4051

    Article  PubMed  CAS  Google Scholar 

  • Dimitrova DS, Gilbert DM (1999) The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Mol Cell 4:983–993

    Article  PubMed  CAS  Google Scholar 

  • Donaldson AD (2005) Shaping time: chromatin structure and the DNA replication programme. Trends Genet 21:444–449

    Article  PubMed  CAS  Google Scholar 

  • Drouin R, Lemieux N, Richer CL (1990) Analysis of DNA replication during S phase by means of dynamic chromosome banding at high resolution. Chromosoma 99:272–280

    Article  Google Scholar 

  • Dutrillaux B, Couturier J, Richer C-L, Viegas-Peguinot E (1976) Sequence of DNA replication in 277 R- and Q-bands of human chromosomes using a BrdU treatment. Chromosoma 58:51–61

    Article  PubMed  CAS  Google Scholar 

  • Edenberg HJ, Huberman JA (1975) Eukaryotic chromosome replication. Annu Rev Genet 9:245–284

    Article  PubMed  CAS  Google Scholar 

  • Englmann A, Clarke LA, Christan S, Amaral MD, Schindelhauer D, Zink D (2005) The replication timing of CFTR and adjacent genes. Chromosome Res 13:183–194

    Article  PubMed  CAS  Google Scholar 

  • Ermakova OV, Nguyen LH, Little RD, Chevillard C, Riblet R, Ashouian N, Birshtein BK, Schildkraut CL (1999) Evidence that a single replication fork proceeds from early to late replicating domains in the IgH locus in a non-B cell line. Mol Cell 3:321–330

    Article  PubMed  CAS  Google Scholar 

  • Ferreira J, Paolella G, Ramos C, Lamond AI (1997) Spatial organization of large-scale chromatin domains in the nucleus: a magnified view of single chromosome territories. J Cell Biol 139:1597–1610

    Article  PubMed  CAS  Google Scholar 

  • Furey TS, Haussler D (2003) Integration of the cytogenetic map with the draft human genome sequence. Hum Mol Genet 12:1037–1044

    Article  PubMed  CAS  Google Scholar 

  • Goldman MA, Holmquist GP, Gray MC, Caston LA, Nag A (1984) Replication timing of genes and middle repetitive sequences. Science 224:686–692

    Article  PubMed  CAS  Google Scholar 

  • Goren A, Cedar H (2003) Replicating by the clock. Nat Rev Mol Cell Biol 4:25–32

    Article  PubMed  CAS  Google Scholar 

  • Habermann FA, Cremer M, Walter J, Kreth G, von Hase J, Bauer K, Wienberg J, Cremer C, Cremer T, Solovei I (2001) Arrangements of macro- and microchromosomes in chicken cells. Chromosome Res 9:569–584

    Article  PubMed  CAS  Google Scholar 

  • Hand R (1978) Eucaryotic DNA: Organization of the genome for replication. Cell 15:317–325

    Article  PubMed  CAS  Google Scholar 

  • Hatton KS, Dhar V, Brown EH, Iqbal MA, Stuart S, Didamo VT, Schildkraut CL (1988) Replication program of active and inactive multigene families in mammalian cells. Mol Cell Biol 8:2149–2158

    PubMed  CAS  Google Scholar 

  • Hiratani I, Leskovar A, Gilbert DM (2004) Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 101:16861–16866

    Article  PubMed  CAS  Google Scholar 

  • Huberman JA, Riggs AD (1966) Autoradiography of chromosomal DNA fibers from Chinese hamster cells. Proc Natl Acad Sci U S A 55:599–606

    Article  PubMed  CAS  Google Scholar 

  • ISCN (1995) An international system for human cytogenetic nomenclature. S. Karger, New York

    Google Scholar 

  • Jackson DA, Pombo A (1998) Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J Cell Biol 140:1285–1295

    Article  PubMed  CAS  Google Scholar 

  • Jacob F, Brenner S, Cuzin F (1964) On the regulation of DNA replication in bacteria. Cold Spring Harb Symp Quant Biol 28:329–348

    Google Scholar 

  • Jeon Y, Bekiranov S, Karnani N, Kapranov P, Ghosh S, MacAlpine D, Lee C, Hwang DS, Gingeras TR, Dutta A (2005) Temporal profile of replication of human chromosomes. Proc Natl Acad Sci U S A 102:6419–6424

    Article  PubMed  CAS  Google Scholar 

  • Jeppesen P, Turner BM (1993) The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell 74:281–289

    Article  PubMed  CAS  Google Scholar 

  • Kennedy BK, Barbie DA, Classon M, Dyson N, Harlow E (2000) Nuclear organization of DNA replication in primary mammalian cells. Genes Dev 14:2855–2868

    Article  PubMed  CAS  Google Scholar 

  • Kim MA, Johannsmann R, Grzeschik K-H (1975) Giemsa staining of the sites replicating DNA early in human lymphocyte chromosomes. Cytogenet Cell Genet 15:363–371

    Article  PubMed  CAS  Google Scholar 

  • Lander ES et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  PubMed  CAS  Google Scholar 

  • Leonhardt H, Rahn H-P, Weinzierl P, Sporbert A, Cremer T, Zink D, Cardoso MC (2000a) Dynamics of DNA replication factories in living cells. J Cell Biol 149:271–279

    Article  PubMed  CAS  Google Scholar 

  • Leonhardt H, Sporbert A, Cardoso MC (2000b) Targeting regulatory factors to intranuclear replication sites. Crit Rev Eukaryot Gene Expr 12:127–133

    Google Scholar 

  • Lercher MJ, Urrutia AO, Hurst LD (2002) Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 31:180–183

    Article  PubMed  CAS  Google Scholar 

  • Li F, Chen J, Izumi M, Butler MC, Keezer SM, Gilbert DM (2001) The replication timing program of the Chinese hamster beta-globin locus is established coincident with its repositioning near peripheral heterochromatin in early G1 phase. J Cell Biol 154:283–292

    Article  PubMed  CAS  Google Scholar 

  • Li F, Chen J, Solessio E, Gilbert DM (2003) Spatial distribution and specification of mammalian replication origins during G1 phase. J Cell Biol 161:257–266

    Article  PubMed  CAS  Google Scholar 

  • Lin CM, Fu H, Martinovsky M, Bouhassira E, Aladjem MI (2003) Dynamic alterations of replication timing in mammalian cells. Curr Biol 13:1019–1028

    Article  PubMed  CAS  Google Scholar 

  • Ma H, Samarabandu J, Devdhar RS, Acharya R, Cheng P-C, Meng C, Berezney R (1998) Spatial and temporal dynamics of DNA replication sites in mammalian cells. J Cell Biol 143:1415–1425

    Article  PubMed  CAS  Google Scholar 

  • MacAlpine DM, Rodriguez HK, Bell SP (2004) Coordination of replication and transcription along a Drosophila chromosome. Genes Dev 18:3094–3105

    Article  PubMed  CAS  Google Scholar 

  • Mahy NL, Perry PE, Bickmore WA (2002a) Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J Cell Biol 159:753–763

    Article  PubMed  CAS  Google Scholar 

  • Mahy NL, Perry PE, Gilchrist S, Baldock RA, Bickmore WA (2002b) Spatial organization of active and inactive genes and noncoding DNA within chromosome territories. J Cell Biol 157:579–589

    Article  PubMed  CAS  Google Scholar 

  • Manders EMM, Stap J, Brakenhoff GJ, van Driel R, Aten JA (1992) Dynamics of three-dimensional replication patterns during S-phase, analysed by double labelling of DNA and confocal microscopy. J Cell Sci 103:857–862

    PubMed  CAS  Google Scholar 

  • Manders EMM, Kimura H, Cook PR (1999) Direct imaging of DNA in living cells reveals the dynamics of chromosome formation. J Cell Biol 144:813–821

    Article  PubMed  CAS  Google Scholar 

  • Mayr C, Jasencakova Z, Meister A, Schubert I, Zink D (2003) Comparative analysis of the functional genome architecture of animal and plant cell nuclei. Chromosome Res 11:471–484

    Article  PubMed  CAS  Google Scholar 

  • Nakamura H, Morita T, Sato C (1986) Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp Cell Res 165:291–297

    Article  PubMed  CAS  Google Scholar 

  • Nakayasu H, Berezney R (1989) Mapping replicational sites in the eucaryotic cell nucleus. J Cell Biol 108:1–11

    Article  PubMed  CAS  Google Scholar 

  • Newlon CS, Theis JF (1993) The structure and function of yeast ARS elements. Curr Opin Genet Dev 3:752–758

    Article  PubMed  CAS  Google Scholar 

  • O’Keefe RT, Henderson SC, Spector DL (1992) Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific α-satellite DNA sequences. J Cell Biol 116:1095–1110

    Article  PubMed  CAS  Google Scholar 

  • Panning MM, Gilbert DM (2005) Spatio-temporal organization of DNA replication in murine embryonic stem, primary, and immortalized cells. J Cell Biochem 95:74–82

    Article  PubMed  CAS  Google Scholar 

  • Pepperkok R, Ansorge W (1995) Direct visualization of DNA replication sites in living cells by microinjection of fluorescein-conjugated dUTPs. Methods Mol Cell Biol 5:112–117

    Google Scholar 

  • Perry P, Sauer S, Billon N, Richardson WD, Spivakov M, Warnes G, Livesey FJ, Merkenschlager M, Fisher AG, Azuara V (2004) A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction. Cell Cycle 3:1645–1650

    PubMed  CAS  Google Scholar 

  • Postberg J, Alexandrova O, Cremer T, Lipps HJ (2005) Exploiting nuclear duality of ciliates to analyse topological requirements for DNA replication and transcription. J Cell Sci 118:3973–3983

    Article  PubMed  CAS  Google Scholar 

  • Raghuraman MK, Winzeler EA, Collingwood D, Hunt S, Wodicka L, Conway A, Lockhart DJ, Davis RW, Brewer BJ, Fangman WL (2001) Replication dynamics of the yeast genome. Science 294:115–121

    Article  PubMed  CAS  Google Scholar 

  • Rountree MR, Bachman KE, Baylin SB (2000) DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet 25:269–277

    Article  PubMed  CAS  Google Scholar 

  • Saccone S, De Sario A, Wiegant J, Raap AK, Della Valle G, Bernardi G (1993) Correlations between isochores and chromosomal bands in the human genome. Proc Natl Acad Sci U S A 90:11929–11933

    Article  PubMed  CAS  Google Scholar 

  • Sadoni N, Langer S, Fauth C, Bernardi G, Cremer T, Turner BM, Zink D (1999) Nuclear organization of mammalian genomes: polar chromosome territories build up functionally distinct higher order compartments. J Cell Biol 146:1211–1226

    Article  PubMed  CAS  Google Scholar 

  • Sadoni N, Cardoso MC, Stelzer EH, Leonhardt H, Zink D (2004) Stable chromosomal units determine the spatial and temporal organization of DNA replication. J Cell Sci 117:5353–5365

    Article  PubMed  CAS  Google Scholar 

  • Schermelleh L (2003) Dynamic organization of chromosomes in the mammalian cell nucleus. PhD Thesis at the Ludwig-Maximilians-Universität München: 1–121

  • Schübeler D, Francastel C, Cimbora DM, Reik A, Martin DIK, Groudine M (2000) Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human β-globin locus. Genes Dev 14:940–950

    PubMed  Google Scholar 

  • Schübeler D, Scalzo D, Kooperberg C, van Steensel B, Delrow J, Groudine M (2002) Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing. Nat Genet 32:438–442

    Article  PubMed  CAS  Google Scholar 

  • Schübeler D, MacAlpine DM, Scalzo D, Wirbelauer C, Kooperberg C, van Leeuwen F, Gottschling DE, O’Neill LP, Turner BM, Delrow J, Bell SP, Groudine M (2004) The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev 18:1263–1271

    Article  PubMed  Google Scholar 

  • Selig S, Okumura K, Ward DC, Cedar H (1992) Delineation of DNA replication time zones by fluorescence in situ hybridization. EMBO J 11:1217–1225

    PubMed  CAS  Google Scholar 

  • Smith ZE, Higgs DR (1999) The pattern of replication at a human telomeric region (16p13.3): its relationship to chromosome structure and gene expression. Hum Mol Genet 8:1373–1386

    Article  PubMed  CAS  Google Scholar 

  • Spada F, Chioda M, Thompson EM (2005) Histone H4 post-translational modifications in chordate mitotic and endoreduplicative cell cycles. J Cell Biochem 95:885–901

    Article  PubMed  CAS  Google Scholar 

  • Sparvoli E, Levi M, Rossi E (1994) Replication clusters may form structurally stable complexes of chromatin and chromosomes. J Cell Sci 107:3097–3103

    PubMed  CAS  Google Scholar 

  • Sporbert A, Gahl A, Ankerhold R, Leonhardt H, Cardoso MC (2002) DNA polymerase clamp shows little turnover at established replication sites but sequential do novo assembly at adjacent origin clusters. Mol Cell 10:1355–1365

    Article  PubMed  CAS  Google Scholar 

  • Thomson I, Gilchrist S, Bickmore WA, Chubb JR (2004) The radial positioning of chromatin is not inherited through mitosis but is established de novo in early G1. Curr Biol 14:166–172

    Article  PubMed  CAS  Google Scholar 

  • Turner BM (2002) Cellular memory and the histone code. Cell 111:285–291

    Article  PubMed  CAS  Google Scholar 

  • Versteeg R, van Schaik BDC, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AHC (2003) The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res 13:1998–2004

    Article  PubMed  CAS  Google Scholar 

  • Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, Goldsworthy M, Powis SH, Ragoussis J et al (2000) Large-scale chromatin organisation of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J Cell Sci 113:1565–1576

    PubMed  CAS  Google Scholar 

  • Walter J, Schermelleh L, Cremer M, Tashiro S, Cremer T (2003) Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol 160:685–697

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Fujiyama A, Ichiba Y, Hattori M, Yada T, Sakaki Y, Ikemura T (2002) Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions. Hum Mol Genet 11:13–21

    Article  PubMed  CAS  Google Scholar 

  • White EJ, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley EJ, Weissman S, Gerstein M, Groudine M, Snyder M, Schubeler D (2004) DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci U S A 101:17771–17776

    Article  PubMed  CAS  Google Scholar 

  • Williams RRE, Azuara V, Perry P, Sauer S, Dvorkina M, Jorgensen H, Roix J, McQueen P, Misteli T, Merkenschlager M, Fisher AG (2006) Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 119:132–140

    Article  PubMed  CAS  Google Scholar 

  • Woodfine K, Fiegler H, Beare DM, Collins JE, McCann OT, Young BD, Debernardi S, Mott R, Dunham I, Carter NP (2004) Replication timing of the human genome. Hum Mol Genet 13:191–202

    Article  PubMed  CAS  Google Scholar 

  • Wyman C, Botchan M (1995) DNA replication. A familiar ring to DNA polymerase processivity. Curr Biol 5:334–337

    Article  PubMed  CAS  Google Scholar 

  • Yunis JJ (1981) Mid-prophase human chromosomes. The attainment of 2000 bands. Hum Genet 56:293–298

    Article  PubMed  CAS  Google Scholar 

  • Yurov YB, Liapunova NA (1977) The units of DNA replication in the mammalian chromosomes: evidence for a large size of replication units. Chromosoma 60:253–267

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Xu F, Hashimshony T, Keshet I, Cedar H (2002) Establishment of transcriptional competence in early and late S phase. Nature 420:198–202

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Ermakova OV, Riblet R, Birshtein BK, Schildkraut CL (2002) Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells. Mol Cell Biol 22:4876–4889

    Article  PubMed  CAS  Google Scholar 

  • Zink D, Cremer T, Saffrich R, Fischer R, Trendelenburg MF, Ansorge W, Stelzer EHK (1998) Structure and dynamics of human interphase chromosome territories in vivo. Hum Genet 102:241–251

    Article  PubMed  CAS  Google Scholar 

  • Zink D, Bornfleth H, Visser A, Cremer C, Cremer T (1999) Organization of early and late replicating DNA in human chromosome territories. Exp Cell Res 247:176–188

    Article  PubMed  CAS  Google Scholar 

  • Zink D, Sadoni N, Stelzer E (2003) Visualizing chromatin and chromosomes in living cells. Methods 29:42–50

    Article  PubMed  CAS  Google Scholar 

  • Zink D, Amaral MD, Englmann A, Lang S, Clarke LA, Rudolph C, Alt F, Luther K, Braz N, Sadoni N, Rosenecker J, Schindelhauer D (2004) Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei. J Cell Biol 166:815–825

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I thank Jeannette Koch (LMU München) for the artwork and for arranging the figures and Dirk Schübeler (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) and Edith Heard (Curie Institute, Paris, France) for their helpful comments. I thank Dean A. Jackson (University of Manchester, UK) and Ana Pombo (Imperial College, London, UK) for the permission to reproduce figures. D.Z. is supported by grants from the VolkswagenStiftung and the Deutsche Forschungsgemeinschaft (SFB/TR 5).

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    Daniele Zink

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Communicated by E.A. Nigg

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Zink, D. The temporal program of DNA replication: new insights into old questions. Chromosoma 115, 273–287 (2006). https://doi.org/10.1007/s00412-006-0062-8

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